Our invention relates to controlled time-release microparticulate active and bioactive compositions (including perfuming compositions) for targeted delivery to surfaces such as skin, hair and fabric and the environment proximate thereto. The active and bioactive materials contained in the microparticulate compositions of our invention have a calculated log10P of between 1 and 8 (P being the n-octanol-water partition coefficient of the active and bioactive materials). Such compositions include the active or bioactive material in single phase solid solution in a wax or polymer matrix also having coated thereon and/or containing a compatible surfactant. Certain combinations of surfactants useful in the practice of our invention are novel, for the surfactants include partially hydrolyzed polyvinyl acetate. Other materials, to wit: tetra(2-hydroxypropyl)ethylenediamine having the structure: 
is not only useful as a surfactant, but also increases the substantivity of fragrances.
Many household products, personal products and health care products contain active and bioactive products which need to be delivered to and deposited on a target surface, i.e., fabric, skin, hair and other living tissues. Once deposited on the target surface, there is a need for the active product, i.e., a fragrance, flavor or drug, to be controllably and sustainably released over a long period of time in an efficacious manner.
Publications in the prior art indicate attempts to fulfill the foregoing needs. However, no engineered coordination of the utilization of the variables concerned has been shown in the prior art whereby, depending on the changing (as a function of time) physical and chemical properties of the surface treated and surrounding environment, the chemical and physical nature of the active and bioactive product (including diffusivities taken alone and in combination with one another in various delivery systems), the controlled time release particle composition, the controlled time release particle size range and the required rate of controlled time release of the active and bioactive product to the surface and environment surrounding the active or bioactive product delivery composition, the delivery system is shown to be capable of being optimally designed and easily and commercially manufactured.
Young, U.S. Pat. No. 4,152,272 issued on May 1, 1979 discloses fabric conditioning compositions containing particles of size 0.1 to 200 microns and of melting point 38xc2x0 C. to 150xc2x0 C. and comprising a wax-like carrier substance and a perfume. The particles are distributed throughout a composition, especially an aqueous fabric softening composition which contains a fabric-substantive cationic surfactant. An example of the cationic surfactant of Young is cetyl trimethyl ammonium bromide cited at column 6, lines 23 and 24. Young, however, shows formation of wax/perfume particles using, for example, a colloid mill as is shown at column 8, lines 60-65.
Domb, U.S. Pat. No. 5,188,837 issued on Feb. 23, 1993 discloses a microsuspension system and method for its preparation. The microsuspension contains lipospheres which are solid, water-insoluble microparticles that have a layer of a phospholipid embedded on their surface. The core of the liposphere is a solid substance to be delivered or a substance to be delivered that is dispersed in an inert solid vehicle such as a wax.
Trinh, et al, U.S. Pat. No. 5,540,853 issued on Jul. 30, 1996 discloses a personal cleansing composition comprising:
(a) from about 0.001% up to about 10% by weight of an enduring perfume composition having at least about 70% components with a calculated log10Pxe2x89xa73 and a boiling point of xe2x89xa7250xc2x0 C.;
(b) from about 0.01% up to about 95% by weight of a surfactant system; and
(c) the balance comprising carrier
wherein the pH is from about 4 up to about 11. Trinh, et al, however, does not disclose a particulate control time release delivery system containing active, bioactive or perfuming materials which have a calculated log10P in the range of from 1 up to about 8. The disclosure of Trinh, et al, U.S. Pat. No. 5,540,853 is incorporated by reference herein.
Somasundaran, et al, U.S. Pat. No. 5,476,660 issued on Dec. 19, 1995 discloses compositions to deposit an active substance on a target surface. The active substance is left on the surface after the product is rinsed off the surface. The preferred deposition is from compositions containing an anionic or nonionic active in the co-presence of an anionic surfactant. The compositions contain carrier particles having a zwitterionic or cationic surface and a plurality of outwardly protruding filaments containing charged organocarbyl groups. The active substance is contained within the carrier particles. Examples of target surfaces are mammalian skin, hair or nails.
Bacon, et al, U.S. Pat. No. 5,652,206 issued on Jul. 29, 1997 discloses a rinse-added fabric softening composition selected from the group consisting of:
I. a solid particulate composition comprising:
(A) from about 50% to about 95% of biodegradable cationic quaternary ammonium fabric softening compound:
(B) from about 0.01% to about 15% of an enduring perfume comprising at least 70% of enduring perfume ingredients selected from the group consisting of: ingredients having a boiling point of at least about 250xc2x0 C. and a ClogP of at least about 3, wherein ClogP is the calculated octanol/water partitioning coefficient as the logarithm to the base 10.logP, said ingredients having a boiling point of at least 250xc2x0 C. and a ClogP of at least about 3 being less than 70% by weight of said enduring perfume so that a perfume with only ingredients having a boiling point of at least about 250xc2x0 C. and a ClogP of at least about 3 will not be an enduring perfume; cis-jasmone; dimethyl benzyl carbinyl acetate; ethyl vanillin; geranyl acetate; xcex1-ionone; xcex2-ionone; xcex3-ionone; KOAVONE(copyright); lauric aldehyde; methyl dihydrojasmonate; methyl nonyl acetaldehyde; xcex3-nonalactone; phenoxy ethyl iso-butyrate; phenyl ethyl dimethyl carbinol; phenyl ethyl dimethyl carbinyl acetate; xcex1-methyl-4-(2-methylpropyl)-benzenepropanal; 6-acetyl-1,1,3,4,4,6-hexamethyl tetrahydronaphthalene; undecylenic aldehyde; vanillin; 2,5,5-trimethyl-2-pentyl-cyclopentanone; 2-tert-butylcyclohexanol; verdox; para-tert-butylcyclohexyl acetate; and mixtures thereof;
(C) optionally, from about 0% to about 30% of dispersibility modifier; and
(D) optionally, from about 0% to about 15% of a pH modifier; and
II. a liquid composition comprising:
(A) from about 0.5% to about 80% of biodegradable cationic fabric softening compound;
(B) from about 0.01% to about 10% of an enduring perfume comprising at least 70% of enduring perfume ingredients selected from the group consisting of: ingredients having a boiling point of at least about 250xc2x0 C. and a ClogP of at least 3, said ingredients having a boiling point of at least about 250xc2x0 C. and a ClogP of at least about 3 being less than 70% by weight of said enduring perfume so that a perfume with only ingredients having a boiling point of at least about 250xc2x0 C. and a ClogP of at least about 3 will not be an enduring perfume; cis-jasmone; dimethyl benzyl carbinyl acetate; ethyl vanillin; geranyl acetate; xcex1-ionone; xcex2-ionone; xcex3-ionone; KOAVONE(copyright); lauric aldehyde; methyl dihydrojasmonate; methyl nonyl acetaldehyde; xcex3-nonalactone; phenoxy ethyl iso-butyrate; phenyl ethyl dimethyl carbinol; phenyl ethyl dimethyl carbinyl acetate; xcex1-methyl-4-(2-methylpropyl)-benzenepropanal; 6-acetyl-1,1,3,4,4,6-hexamethyl tetrahydronaphthalene; undecylenic aldehyde; vanillin; 2,5,5-trimethyl-2-pentyl-cyclopentanone; 2-tert-butylcyclohexanol; verdox; para-tert-butylcyclohexyl acetate; and mixtures thereof;
(C) optionally, from about 0% to about 30% of dispersibility modifier; and
(D) the balance comprising a liquid carrier selected from the group consisting of water, C1-4 monohydric alcohol; C2-6 polyhydric alcohol; propylene carbonate; liquid polyethylene glycols; and mixtures thereof;
and wherein the dispersibility modifier affects the viscosity, dispersibility or both.
The Bacon, et al reference does not disclose or infer the control time release system of our invention wherein the particles, each consisting of a solid solution of a hydrophobic polymer and/or a hydrophobic wax contain and deliver active, bioactive or fragrance materials to a solid surface and to the environment surrounding same which active, bioactive and perfuming materials have a calculated log10P in the range of from 1 up to about 8.
Kamel, et al, U.S. Pat. No. 4,919,841 issued on Apr. 24, 1990 discloses a process for preparing encapsulated active particles by the steps of: dispersing active materials in molten wax; emulsifying the active/wax dispersion in an aqueous surfactant solution for no longer than 4 minutes; quenching the capsules by cooling; and retrieving solidified capsules. Examples of active materials are fragrances. Kamel, et al, however, does not show the specific formation of single phase solid solutions of matrix materials containing at least one hydrophobic polymer and/or at least one hydrophobic wax having dissolved therein at least one hydrophobic fragrance material controllably time releasable therefrom and having a calculated log10P in the range of from about 1 up to about 8.
Henkel (Wahle, et al), PCT Published Application No. 95/11936 published on Oct. 20, 1994 discloses finely dispersed wax dispersions with a long shelf life which can be obtained by heating: (A) 10 to 80 weight percent of a wax with (B) 0.5 to 30 weight percent of a hydrophilic nonionic dispersant with an HLB value of 8 to 18 and (C) 1 to 30 weight percent of a hydrophobic co-dispersant from the group of fatty alcohols with 12-22 carbon atoms or the partial esters of polyols with 3-6 carbon atoms with fatty acids with 12-22 carbon atoms, and then heating the dispersion obtained to a temperature within or above the phase inversion point or producing a dispersion directly at this temperature and subsequently cooling the dispersion to a temperature below the phase inversion range. PCT Application No. 95/11936 does not, however, disclose the particulate composition of our invention containing a single phase solid solution of a hydrophobic polymer and/or a hydrophobic wax having dissolved therein at least one hydrophobic fragrance material, capable of delivering the fragrance material to a surface and to the environment surrounding the particulate composition and wherein the fragrance has a log10P of between about 1 and about 8.
Donbrow, Microcapsules and Nanoparticles in Medicine and Pharmacy, Chapter 6, xe2x80x9cNANOPARTICLESxe2x80x94PREPARATION AND APPLICATIONSxe2x80x9d, Jorg Kreuter (pages 126-148), CRC Press, 1992, discloses the production of nanoparticles containing bioactive materials by means of emulsion polymerization. The Donbrow reference does not explicitly or implicitly disclose the novel process for preparing the novel compositions of matter of our invention.
Adeyeye et al, xe2x80x9cDevelopment and Evaluation of Sustained-Release Ibuprofen Wax Microspheres. I. Effect of Formulation Variables on Physical Characteristicsxe2x80x9d, Pharm. Res. (1991), Volume 8, No. 11, pages 1377-1383, discloses the use of a congealable disperse phase encapsulation method for preparing sustained-release ibuprofen-wax microspheres. The microspheres are prepared with paraffin wax such as ceresine and mycrocrystalline waxes using polyvinylpyrrolidone as a dispersant and using stearyl alcohol as a wax modifier. Adeyeye, et al does not infer or disclose the microparticulate compositions of matter of our invention containing active or bioactive materials having a calculated log10P in the range of from 1 up to about 8.
Thus, nothing in the prior art discloses compositions for effecting the targeted delivery of bioactive or active substances to substantially solid surfaces wherein a substance comprises at least one substantially ellipsoidal hydrophobic particle consisting essentially of a single phase solid solution of a hydrophobic polymer or a hydrophobic wax having dissolved therein at least one active or bioactive material and having proximate to substantially the entirety of its outer surface a substantially hydrophilic surfactant wherein the calculated log10P of the active or bioactive substance is in the range of from about 1 up to about 8.
Our invention concerns controlled time-release microparticulate active and bioactive compositions (including perfuming compositions) for targeted delivery to surfaces such as skin, hair and fabric and the environment proximate thereto, where the active and bioactive materials have a calculated log10P of between 1 and 8 (P being the n-octanol-water partition coefficient). Such compositions include the active or bioactive material in single phase solid solution in a wax or polymer matrix also having coated thereon and/or containing a compatible surfactant. Our invention is also directed to processes and apparatus for preparing such compositions and processes for using same. Furthermore, certain component(s) of the above-mentioned compositions in combination with one another are novel; both combinations containing partially hydrolyzed polyvinyl acetate having a degree of hydrolysis of between about 73% up to about 99% and having a molecular weight in the range of from about 5,000 up to about 67,000. Our invention is also directed to novel compositions having high perfume substantivity including the compound: tetra(2-hydroxypropyl)ethylenediamine having the structure: 
More particularly, our invention is directed to a composition for effecting the targeted delivery of a bioactive or active substance to a substantially solid surface comprising at least one substantially ellipsoidal hydrophilic particle having a continuous outer surface and an internal matrix volume consisting essentially of:
(i) a single phase solid solution of a matrix material which is in the alternative at least one of a hydrophobic polymer and/or at least one hydrophobic wax, each of which polymer and wax has a melting point in the range of from about 35xc2x0 C. up to about 120xc2x0 C. at 1 atmosphere pressure, having dissolved therein at least one active or bioactive substance (for example, a fragrance material) which is hydrophobic, said solid solution having an outer surface and an internal matrix volume; and
(ii) proximate to substantially the entirety of said outer surface a substantially hydrophilic surfactant.
The active or bioactive material, such as a fragrance material, having a calculated log10P in the range of from about 1 up to about 8 wherein P is the partition coefficient of the active or bioactive material between n-octanol and water; with the hydrophobic particle having an outside diameter in the range of from about 0.50 up to about 20 microns; the concentration of active or bioactive material in the polymer or the wax being from about 5% up to about 60% by weight of the particle; the weight percent of the surfactant being from about 0.01% up to about 5% by weight of the particle; with the wax, the surfactant and the polymer each being nonreactive with the bioactive or active material and one another.
A preferred composition of our invention is one where the permeation rate of the active or bioactive material, such as the fragrance material, through the wax or the polymer is in the range of from about       10          -      8        ⁢      xe2x80x83    ⁢            mg      -      mm                      cm        2            -      min      
up to about   8  xc3x97      10          -      3        ⁢      xe2x80x83    ⁢            mg      -      mm                      cm        2            -      min      
as determined by the IFF permeation test as more fully described herein in the xe2x80x9cDETAILED DESCRIPTION OF THE DRAWINGSxe2x80x9d section, infra.
As stated, supra, proximate to substantially the entirety of the outer surface of the substantially ellipsoidal hydrophobic particle is a substantially hydrophilic surfactant. More specifically, the following three cases exist concerning the location of the surfactant:
(a) the substantially hydrophilic surfactant may be substantially entirely coated on and fixedly bonded to the entirety of the outer surface of the single phase solid solution in the form of a continuous submicron layer of surfactant; or
(b) the substantially hydrophilic surfactant may be located proximate to and immediately, substantially beneath the entirety of the outer surface of the solid solution and substantially within the said internal matrix volume; and
(c) the substantially hydrophilic surfactant is both (a) substantially, entirely coated on and fixedly bonded to the entirety of the outer surface of the single phase solid solution in the form of a continuous submicron layer of surfactant and (b) located proximate to and immediately, substantially beneath the entirety of the outer surface of the solid solution and substantially within the internal matrix volume.
With respect to the surfactant, the surfactant may be a cationic surfactant, and the particle would therefore be positively charged; the surfactant may be an anionic surfactant, and the particle would be negatively charged; the surfactant could be a nonionic surfactant, and the particle would have a neutral charge; and the surfactant is a zwitterionic surfactant, and the particle has a variable charge.
Examples of surfactants particularly preferred in the practice of our invention are as follows:
(a) the cationic modified starch, RediBOND(copyright) 5320 (trademark of the National Starch Company of Bridgewater, N.J.), in admixture with partially hydrolyzed polyvinyl acetate having a degree of hydrolysis of between about 73% up to about 99% and having a molecular weight in the range of from about 5,000 up to about 67,000;
(b) the substance tetra(2-hydroxypropyl)ethylenediamine (marketed, for example, as QUADROL(copyright) Polyol, and having the structure: 
(c) cetyl trimethyl ammonium halide, including cetyl trimethyl ammonium chloride having the structure: 
(d) a quaternary ammonium polysilane derivative having the structure: 
xe2x80x83wherein R is the moiety having the structure:
CH3xe2x80x94[CH2]xxe2x80x94;
wherein x is an integer of from 10 up to 100 and m is an integer of from 10 up to 100 in admixture with partially hydrolyzed polyvinyl acetate being hydrolyzed to the extent of from about 73% up to about 99% and having a molecular weight in the range of from about 5,000 up to about 67,000; and
(e) the cationic polysaccharide derivative defined according to the structure: 
xe2x80x83wherein n is an integer of from 1 up to 3; R11 and R12 are independently an alkyl, aryl, aralkyl or alkaryl group when n is 1; R11 or R12 is one of the groups when n is 2; or R11 and R12 are not present when n is 3; and wherein the moiety xe2x80x9cSACCHxe2x80x9d represents a starch or cellulose moiety.
The weight ratio of cationic modified starch:partially hydrolyzed polyvinyl acetate, is preferably in the range of from about 2:1 up to about 1:2, with a ratio of 1:2 being preferred. The weight ratio of the quaternary ammonium polysilane derivative:partially hydrolyzed polyvinyl acetate, is also preferably in the range of from about 2:1 up to about 1:2, with a weight ratio of 1:2 being preferred.
The mixtures of the cationic modified starch and partially hydrolyzed polyvinyl acetate as well as the quaternary ammonium polysilane derivative and partially hydrolyzed polyvinyl acetate are novel mixtures.
The matrix material which may be at least one hydrophobic polymer and/or at least one hydrophobic wax useful in the practice of our invention is preferably at least one of the following materials:
(a) polyamides having a molecular weight in the range of from about 6,000 up to about 12,000, for example, MACROMELT(copyright) 6030 manufactured by the Henkel Ag. of Dusseldorf, Germany (other examples being set forth in Lindauer, et al, U.S. Pat. No. 4,184,099 issued on Jan. 15, 1980, the specification for which is incorporated by reference herein and including the VERSALON(copyright) line of polyamide polymers manufactured by the Henkel Corporation of Minneapolis, Minn.);
(b) synthetic and natural carnauba wax;
(c) synthetic and natural candelilla wax;
(d) mixtures of cetyl palmitate (marketed, for example, as CUTINA(copyright) wax) with carnauba wax;
(e) mixtures of cetyl palmitate and candelilla wax;
(f) ozokerite wax;
(g) ceresin wax; and
(h) low density polyethylene wax having a molecular weight in the range of from about 500 up to about 6,000.
Different combinations of waxes and surfactants are preferred for different fragrance compositions having different overall calculated log10P for different applications, for example, hair care or fabric care.
The maximum vapor pressure for the active or bioactive material in the composition of our invention should be 4.1 mm/Hg at 30xc2x0 C. In the event that the active material is a fragrance material, it is preferred that when the fragrance material has topnote components, middle note components and bottom note components, the vapor pressure ranges for each of these three groups of components should be as follows:
(a) with respect to the bottom note components, the vapor pressure range should be from 0.0001 mm/Hg up to 0.009 mm/Hg at 25xc2x0 C.;
(b) with respect to the middle note components, the vapor pressure range of the middle note components should be from 0.01 mm/Hg up to 0.09 mm/Hg at 25xc2x0 C.; and
(c) with respect to the topnote components, the vapor pressure range of the bottom note components should be from 0.1 mm/Hg up to 2.0 mm/Hg at 25xc2x0 C.
An example of such a fragrance as described, supra, is as follows:
The particles of the composition of our invention may contain or have coated thereon (or both) surfactants having (i) a sufficient charge per molecule of surfactant and (ii) a sufficient concentration of surfactant in each particle so that the electrostatic charge density on the surface of each particle will be sufficient to cause adherence of the particle to a given surface, such as hair, mammalian skin or a fabric.
While using the material, tetra(2-hydroxypropyl)ethylenediamine having the structure: 
as a surfactant, we have determined that this material is also surprisingly useful in increasing substantivity of fragrances and aroma chemicals when the rate ratio of tetra(2-hydroxypropyl)ethylenediamine:fragrance material is from about 2:15 up to about 4:5. Examples of materials for which the fragrance substantivity will be increased to an extent of greater than about 50% are as follows:
(a) GALAXOLIDE(copyright), a mixture of compounds having the structures: 
(b) geraniol having the structure: 
(c) xcex2-pinene having the structure: 
(d) n-octanal having the structure: 
(e) dihydromyrcenol having the structure: 
(f) KOAVONE(copyright) (trademark of International Flavors and Fragrances Inc. of New York, N.Y.) having the structure: 
(g) eugenol having the structure: 
As indicated, supra, the range of permeation rates of the active and bioactive materials through the wax or polymer of the solid solution-containing particles of our invention is in the range of from about       10          -      8        ⁢      xe2x80x83    ⁢            mg      -      mm                      cm        2            -      min      
up to about   8  xc3x97      10          -      3        ⁢      xe2x80x83    ⁢                    mg        -        mm                              cm          2                -        min              .  
Specifically, the following materials having the following calculated log10P also have the following permeation rates through various waxes and polymers useful in the practice of our invention:
In practicing our invention, the partially hydrolyzed polyvinyl acetate, also termed xe2x80x9cpolyvinyl alcoholxe2x80x9d where the polyvinyl acetate is hydrolyzed to an extent of from about 73% up to about 99%, is prepared by means of any of Examples I-XIV of U.S. Pat. No. 5,051,222 issued on Sep. 24, 1991, the specification for which is incorporated by reference herein. Thus, the polyvinyl alcohol or the partially hydrolyzed polyvinyl acetate is prepared first by polymerizing (via a xe2x80x9cfree radicalxe2x80x9d polymerization mechanism) vinyl acetate having the formula: 
according to the reaction: 
thereby forming a polyvinyl acetate wherein x+y are such that the number average molecular weight of the final product is between 5,000 and 67,000. The resulting polyvinyl acetate having the formula: 
is then hydrolyzed first to form a partially hydrolyzed polyvinyl acetate according to the reaction; 
or a mixture of polyvinyl alcohol and partially hydrolyzed polyvinyl acetate according to the reaction: 
If desired, the partially hydrolyzed polyvinyl acetate may be further hydrolyzed to form polyvinyl alcohol with very few acetyl groups present (thereby forming, for example, 99% hydrolyzed polyvinyl acetate) according to the reaction: 
In any event, the ratio of acetyl moieties to hydroxyl moieties is less than about 1:3 in the structure: 
and x and y are defined whereby x+y gives rise to a polymer that has a number average molecular weight of between about 5,000 and 67,000.
When creating particles having 10% candelilla wax and 10% fragrance (making up, for example, a fabric softener containing 0.72% fragrance) using surfactants containing both hydrolyzed polyvinyl acetate (99% hydrolzyed) and either the quaternary ammonium polysilane derivatives defined according to the structure: 
wherein R is the moiety: CH3xe2x80x94[CH2]xxe2x80x94 and wherein m is an integer of from 10 up to 100 and wherein x is an integer of from 10 up to 100, or the cationic modified starch, RediBOND(copyright) 5320 (trademark of National Starch Inc. of Bridgewater, N.J.), the following table shows the differences in fragrance intensity on a scale of 1-10:
Our invention is also directed to a process for fragrancing a perfumable material having a substantially solid surface, such as hair, fabric and mammalian skin, comprising the step of contacting said solid surface of said perfumable material with at least one particle as defined, supra. When carrying out this process, the intensity of fragrancing, xcex94A, is governed by the algorithm:       Δ    ⁢          xe2x80x83        ⁢    A    =      α    ⁢                  ∑                  k          =          1                P            ⁢              xe2x80x83            ⁢                        ∑                      j            =            1                    Q                ⁢                  xe2x80x83                ⁢                              ∑                          i              =              1                        n                    ⁢                      xe2x80x83                    ⁢                                    B              k                        ⁢                          xe2x80x83                        ⁢                          M              oj                        ⁢                          xe2x80x83                        ⁢                          (                              1                -                                  ⅇ                                                                                    -                        3                                            ⁢                                              D                                                  j                          ⁢                                                      xe2x80x83                                                                                              ⁢                                              xe2x80x83                                            ⁢                                              θ                        2                                                                                    2                      ⁢                                              R                        i                        2                                                                                                        )                                          
wherein xcex1 is a constant, xcex2k is the individual and multiple threshold values of the Q components of the fragrance material within the microparticle being controllably released (the number of threshold values is xe2x80x9cPxe2x80x9d since not only are individual components measured for their thresholds, but pairs and triplets of fragrance materials are measured for their thresholds also); the symbol Moj is the initial number of gram moles of one of Q fragrance components in the particle; Dj is the diffusivity of each of Q fragrance components in the particle; xcex8 is the time during which the particle diffusably and controllably releases the fragrance to the solid surface and environment surrounding the particle; and Ri is the radius of n particles. The aroma intensity created from one particle is shown by the equation:       Δ    ⁢          xe2x80x83        ⁢          A      p        =      α    ⁢          xe2x80x83        ⁢                  ∑                  k          =          1                P            ⁢              xe2x80x83            ⁢                        ∑                      j            =            1                    Q                ⁢                  xe2x80x83                ⁢                              B            k                    ⁢                      xe2x80x83                    ⁢                      M            oj                    ⁢                      xe2x80x83                    ⁢                                    (                              1                -                                  ⅇ                                                                                    -                        3                                            ⁢                                              D                                                  j                          ⁢                                                      xe2x80x83                                                                                              ⁢                                              xe2x80x83                                            ⁢                                              θ                        2                                                                                    2                      ⁢                                              R                        2                                                                                                        )                        .                              
The aroma intensity created by n particles having an average radius {overscore (R)} is shown by the equation:       Δ    ⁢          xe2x80x83        ⁢          A              EST        .              =      α    ⁢          xe2x80x83        ⁢    n    ⁢          xe2x80x83        ⁢                  ∑                  k          =          1                P            ⁢              xe2x80x83            ⁢                        ∑                      j            =            1                    Q                ⁢                  xe2x80x83                ⁢                              M            oj                    ⁢                      xe2x80x83                    ⁢                                    (                              1                -                                  ⅇ                                                                                    -                        3                                            ⁢                                              D                                                  j                          ⁢                                                      xe2x80x83                                                                                              ⁢                                              xe2x80x83                                            ⁢                                              θ                        2                                                                                    2                      ⁢                                              R                        2                                                                                                        )                        .                              
The foregoing equations are derived using the differential equations:       (                  ∂                  C          j                            ∂        θ              )    =                    D        j            ⁢              xe2x80x83            ⁢              (                                            ∂                              C                j                                                                    2                                                    ∂                              x                2                                              +                                    ∂                              C                j                                                                    2                                                    ∂                              y                2                                              +                                    ∂                              C                j                                                                    2                                                    ∂                              z                2                                                    )            ⁢              xe2x80x83            ⁢      and      ⁢              xe2x80x83            ⁢              (                              ∂                          M              j                                            ∂            θ                          )              =          -                                                  D              j                        ⁢                          xe2x80x83                        ⁢                          M              j                        ⁢                          xe2x80x83                        ⁢                          A              j                        ⁢                          xe2x80x83                        ⁢            θ                                              V              i                        ⁢                          xe2x80x83                        ⁢                          R              i                                      .            
The rate of change with respect to time of the aromatization, xcex94A is shown by the equation:                     ⅆ        Δ            ⁢              xe2x80x83            ⁢      A              ⅆ      θ        =            ∑              k        =        1            P        ⁢          xe2x80x83        ⁢                  ∑                  j          =          1                Q            ⁢              xe2x80x83            ⁢                        ∑                      i            =            1                    n                ⁢                  xe2x80x83                ⁢                              B            k                    ⁢                                    {                                                                                          M                      oj                                        ⁢                                          xe2x80x83                                        ⁢                                          D                      j                                        ⁢                                          xe2x80x83                                        ⁢                    θ                                    ∝                                                  R                  i                  2                                            }                        ·                                          [                                                      4                    ⁢                                          e                                                                        -                                                      3                            2                                                                          ⁢                                                  xe2x80x83                                                ⁢                                                                                                            D                              j                                                        ⁢                                                          xe2x80x83                                                        ⁢                                                          θ                              2                                                                                                            R                            i                            2                                                                                                                                -                                      3                    ⁢                                          e                                                                                                    -                            3                                                    ⁢                                                      D                            j                                                    ⁢                                                      xe2x80x83                                                    ⁢                                                      θ                            2                                                                                                    R                          2                                                                                                                    ]                            .                                          
In the foregoing compositions, various grades of partially hydrolyzed and substantially fully hydrolyzed forms of hydrolyzed polyvinyl acetate can be used, to wit:
Additional equations concerning the diffusion of the active or bioactive product from the particulate compositions of our invention are derived using the teachings of Peppas, et al, Journal of Controlled Release, Volume 40 (1996), pages 245-250 and entitled xe2x80x9cControlled release of fragrances from polymers I. Thermodynamic analysisxe2x80x9d and from the text entitled DIFFUSION IN POLYMERS edited by P. Neogi, published 1996 by Marcel Dekker, Inc. at pages 165-169 (chapter by Duda and Zielinski entitled xe2x80x9cFREE-VOLUME THEORYxe2x80x9d and the subchapter entitled xe2x80x9cMulticomponent Diffusionxe2x80x9d. Each of the foregoing references is incorporated by reference herein.
Our invention is also directed to a process for preparing hydrophobic active ingredient- or bioactive ingredient-containing compositions as defined, supra, comprising the steps of:
(i) intimately admixing at least one hydrophobic active ingredient or bioactive ingredient material with at least one hydrophobic polymer and/or at least one hydrophobic wax to form a first mixture at a temperature greater than or equal to the melting point of said polymer or said wax or, in the case of mixtures, the melting point of the highest melting polymer or wax in the mixture;
(ii) intimately admixing a surfactant (as defined, supra) with an aqueous composition comprising water (for example, a mixture of sodium chloride and water or a mixture of propylene glycol and water or water itself) to form a second mixture which is an aqueous solution (for example, a solution of sodium chloride in water or a solution of propylene glycol in water);
(iii) blending said first mixture and said second mixture at a temperature in the range of from about 60xc2x0 C. up to the boiling point at atmospheric pressure of the aqueous composition (for example, water boiling at 100xc2x0 C. or a mixture of water and propylene glycol boiling at 120xc2x0 C.) whereby a microemulsion is formed; and
(iv) causing the hydrophobic active ingredient- or bioactive ingredient (e.g., perfume)-containing composition in the solid phase to form as an aqueous suspension of solid phase particles (as by cooling to 25xc2x0 C.)
wherein the weight percent of active ingredient or bioactive ingredient (e.g., fragrance composition or aroma chemical) for forming said first mixture is in the range of from about 5% up to about 60% by weight of said first mixture; wherein the weight percent of surfactant in the second mixture is from about 0.01% up to about 5% by weight of said second mixture. In fact, the cooling step, cooling the aqueous suspension, can be carried out at a temperature of from about 10xc2x0 C. up to about 30xc2x0 C.
The foregoing process is carried out preferably using a homogenizer and/or a rotor/stator high shear mixer. Examples of a homogenizer useful in the practice of this aspect of our invention are laboratory homogenizer models 15MR and 31MR manufactured by APV Gaulin, Inc. of 44 Garden Street, Everett, Mass. 02149. Examples of rotor/stator high shear mixers are the high shear in-line mixers manufactured by Silverson Machines, Inc., P.O. Box 589, 355 Chestnut Street, East Long Meadow, Mass. 01028 and by the Scott Process Equipment Corporation, P.O. Box 619, Sparta, N.J. 07871. The aforementioned homogenizers and rotor/stator high shear mixers can be used in conjunction with one another, with the rotor/stator high shear mixers being used first and then in order to bring the particle size down further, the resulting emulsion is then further homogenized using the homogenizers such as laboratory homogenizers, models 15MR and 31MR.
The details of the aforementioned homogenizers and rotor/stator high shear mixers are set forth in the xe2x80x9cDETAILED DESCRIPTION OF THE DRAWINGSxe2x80x9d section, infra.
Our invention is also intended to cover a process for preparing the hydrophobic active or bioactive ingredient-containing compositions discussed, supra (e.g., perfume compositions), comprising the steps of:
(i) intimately admixing at least one hydrophobic active or bioactive material (e.g., perfume composition) with (a) at least one hydrophobic polymer and/or at least one hydrophobic wax and (b) at least one surfactant to form a first single liquid phase mixture at a temperature greater than or equal to the melting point of said polymer or said wax or, in the case of mixtures, the melting point of the highest melting polymer or wax in the mixture;
(ii) blending said first single liquid phase mixture with an aqueous composition comprising water (for example, water itself or a mixture of propylene glycol and water or a mixture of sodium chloride and water, for example, a 5% sodium chloride solution or a 20% aqueous propylene glycol solution) whereby a microemulsion is formed; and
(iii) causing the hydrophobic active or bioactive ingredient-containing composition (e.g., a perfume-containing composition or an aroma chemical-containing composition) in the solid phase to form as an aqueous suspension of solid phase particles (for example, cooling the resulting suspension to a temperature in the range of from about 10xc2x0 C. up to about 30xc2x0 C.)
wherein the weight percent of active ingredient or bioactive ingredient for forming the first mixture is in the range of from about 5% up to about 60% by weight of said first mixture; and wherein the weight percent of surfactant in the first mixture is from about 0.01% up to about 5% by weight of the first mixture.
Again, as stated, supra, with respect to the first-described process for preparing hydrophobic active ingredient- or bioactive ingredient-containing compositions of our invention, the blending step is carried out using a homogenizer and/or a rotor/stator high shear mixture as described in detail, supra, and as exemplified in detail, supra, and as described in detail in the DETAILED DESCRIPTION OF THE DRAWINGS section, infra.
Our invention is also directed to apparatus for carrying out the aforementioned processes for preparing the hydrophobic active ingredient- or bioactive ingredient-containing compositions. This apparatus comprises:
(i) means for intimately admixing at least one hydrophobic active ingredient- or bioactive ingredient-containing material with at least one hydrophobic polymer or at least one hydrophobic wax to form a first single liquid phase mixture at a temperature greater than or equal to the melting point of said polymer or said wax or, in the case of mixtures, the highest melting component of the mixture;
(ii) means for intimately admixing a surfactant with an aqueous composition comprising water to form a second mixture which is an aqueous solution (for example, using a homogenizer or rotor/stator high shear mixer);
(iii) means for blending said first mixture and said second mixture at a temperature of between 60xc2x0 C. and the boiling point of the aqueous composition at atmospheric pressure whereby a microemulsion is formed (for example, using the homogenizer and/or the rotor/stator high shear mixer as described, supra); and
(iv) means for causing the hydrophobic active ingredient- or bioactive ingredient-containing composition in the solid phase to form as an aqueous suspension of solid phase particles (for example, using cooling means to cool the mixture to 10-30xc2x0 C., for example, using apparatus equipped with cooling coils).
Additional apparatus for preparing the hydrophobic active or bioactive ingredient-containing compositions of our invention comprise:
(i) means for intimately admixing at least one hydrophobic active ingredient- or bioactive ingredient-containing composition with (a) at least one hydrophobic polymer and/or at least one hydrophobic wax and (b) at least one surfactant to form a first single liquid phase mixture at a temperature greater than or equal to the melting point of said polymer or said wax or, in the case of mixtures, the melting point of the highest melting of the materials in the mixture;
(ii) means for blending said first single liquid phase mixture with an aqueous composition comprising water whereby a microemulsion is formed (for example, using the homogenizer and/or the rotor/stator high shear mixer as described, supra); and
(iii) means for causing the hydrophobic active ingredient- or bioactive ingredient-containing composition in the solid phase to form as an aqueous suspension of solid phase particles (for example, cooling coils to cool the suspension to a temperature of between 10xc2x0 C. and 30xc2x0 C.).